Rare variant models for complex disorders. The schematic shows two models for the genetic etiology of complex disorders. Circles represent rare variants present that are either de novo or inherited from a parent. On the left, individual high-effect de novo variants are strongly associated with a phenotype of interest. On the right, rare variants within an individual combine in multiple ways and contribute toward distinct phenotypes. The thickness of the connecting lines denotes effect sizes, and an affected individual can carry multiple oligogenic combinations of rare variants, each of which contributes to the same or distinct phenotypes. This extension of the oligogenic model enables further dissection of the genetic architecture of complex disorders.
